Capacity for large language model chatbots to aid in orthopedic management, research, and patient queries.

Large language model (LLM) chatbots possess a remarkable capacity to synthesize complex information into concise, digestible summaries across a wide range of orthopedic subject matter. As LLM chatbots become widely available they will serve as a powerful, accessible resource that patients, clinicians, and researchers may reference to obtain information about orthopedic science and clinical management. Here, we examined the performance of three well-known and easily accessible chatbots-ChatGPT, Bard, and Bing AI-in responding to inquiries relating to clinical management and orthopedic concepts. Although all three chatbots were found to be capable of generating relevant responses, ChatGPT outperformed Bard and BingAI in each category due to its ability to provide accurate and complete responses to orthopedic queries. Despite their promising applications in clinical management, shortcomings observed included incomplete responses, lack of context, and outdated information. Nonetheless, the ability for these LLM chatbots to address these inquires has largely yet to be evaluated and will be critical for understanding the risks and opportunities of LLM chatbots in orthopedics.

A vertebral skeletal stem cell lineage driving metastasis.

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.

Intermittent parathyroid hormone increases stability and improves osseointegration of initially unstable implants.

AIMS: To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. METHODS: 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. RESULTS: iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). CONCLUSION: iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260-269.

Head-to-Head Comparison of Kinematic Alignment Versus Mechanical Alignment for Total Knee Arthroplasty.

BACKGROUND: Seeing as there are many alignment strategies for total knee arthroplasty (TKA), we need to determine differences between them in a rigorous scientific way. Therefore, we sought to compare perioperative and postoperative functional outcomes in patients undergoing TKA for varus osteoarthritis with a mechanical alignment target vs a kinematic alignment target, both executed with the same implant and same technological guidance. METHODS: One hundred consecutive patients who underwent TKA using a mechanical alignment technique were 1:1 matched to 100 patients who underwent TKA using a kinematic alignment (KA) technique, using the same implant and robotic technology. Patient-reported outcomes were measured postoperatively at 1 and 2 years. Power analysis revealed 94 patients to detect a significant difference. RESULTS: Mean Visual Analog Scale scores were higher in the mechanical alignment group during the first 6 weeks (P = .04), but statistically similar at 1 year. Six-week Veterans RAND 12 Item Health Survey mental and physical components were statistically similar (P = .1). Patients did not differ in 6-week or 1-year knee range of motion (P > .43). Knee Injury and Osteoarthritis Outcome Score Joint Replacement was significantly better in the KA group at 6 weeks, 1 year, and 2 years (P = .09). Forgotten Joint Score at 1 and 2 years postoperatively were significantly higher in the KA group (P < .001). CONCLUSION: Patients undergoing TKA with KA experienced less pain in 6 weeks after surgery, and higher Forgotten Joint Scores at 1 and 2 years postoperatively. Alternative TKA alignment and balancing strategies should be considered to increase patient satisfaction.

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Accuracy of acetabular cup placement positively correlates with level of training.

BACKGROUND: Accurate acetabular component placement may reduce the risk of complication after total hip arthroplasty (THA). While surgeon experience and volume may reduce outliers, little is known how cup positioning accuracy and consistency relates to level of training (resident, fellow, attending) and whether trainee level impacts the magnitude and direction of cup placement errors. METHODS: Ninety patients undergoing posterolateral computer-assisted navigation THA were included for analysis. All surgery was performed by two fellowship-trained orthopaedic surgeons and assisted by a trainee (orthopedic resident (PGY 1-5) or fellow in adult reconstruction). In order to determine accuracy of cup placement in trainees and attendings, we used computer navigation to determine freehand cup placement by the trainee, then by the attending surgeon. Final cup inclination and version were determined and recorded by computer-assisted surgical navigation. Comparison of consistency in cup inclination and anteversion was made on values obtained by residents, fellows, and attendings and final values provided by the navigation system. In addition, to assess the role of training and repetition, acetabular cup inclination and version were compared between fellows during the first half and the second half of their training year. All comparisons were performed with the Student t-test except for comparison of rate of deviation from the safe zone, which were performed with the chi-square test. The level of significance was defined as p values ≤ 0.05 with 95% confidence interval, and trend toward significance was defined as p values ≤ 0.1. RESULTS: Inclination deviation from the final position and cup version deviation from the final position were statistically significant between resident vs attendings (p < 0.001 (inclination), p < 0.001 (version)), fellow vs attendings (p < 0.001 (inclination), p < 0.001 (version)), and all trainee vs attendings (p < 0.001 (inclination), p < 0.001 (version)). In all comparisons, the attending surgeons placed the cup closer to the final cup position than both resident and fellows. Proportion of inclination deviation from the safe zone of residents was significantly higher than of attendings (p < 0.001) but no significant difference was observed between fellows and attending (p = 1.00). Compared to residents, fellows demonstrated lower proportion of inclination deviation from the safe zone of 3.3% vs 23.3% for fellows vs residents (p = 0.002) and tended to implant the cups in a more horizontal position (45.6 ± 6.6° [SD] and 42.7 ± 4.3°, respectively, p = 0.04). Compared to fellow, residents tended to implant the cup in a more anteverted position than the final cup version (9.6 ± 6.7° and 6.74 ± 5.6° [SD], p = 0.034). There was no statistically significant difference in cup position between attendings' free-hand and final (computer assisted) cup placement. CONCLUSION: Accurate and consistent acetabular cup placement improves with level of training. Accurate and consistent acetabular cup version is harder to master as compared to acetabular cup inclination.

Outpatient Surgical Fixation of Proximal Humerus Fractures Can Be Performed Without Increased Rates of Short-Term Complications or Readmissions.

OBJECTIVE: To delineate differences in short-term complications between outpatient versus inpatient open reduction and internal fixation (ORIF) of proximal humerus fractures. DESIGN: Retrospective database review. SETTING: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients in the National Surgical Quality Improvement Program database with proximal humerus fractures from 2005 to 2017. INTERVENTION: Proximal humerus fracture ORIF. MAIN OUTCOME MEASUREMENTS: Thirty-day readmission, reoperation, thromboembolic events, and other complications. RESULTS: In total, 920 outpatient and 2490 inpatient ORIF cases were identified. The proportion of outpatient proximal humerus fracture ORIF increased throughout the years from 6.67% in 2007 to 34.89% in 2017. Each outpatient case was propensity-score-matched with one inpatient case by age, sex, functional status, American Society of Anesthesiologists classification, smoking status, diabetes mellitus type, hypertension, chronic obstructive pulmonary disease, and dyspnea on exertion. After matching, there were 920 outpatient and 920 inpatient cases. Statistical analysis revealed no significant difference in complications including reoperation (1.63% vs. 2.50%), thromboembolic events (0.65% vs. 0.65%), and 30-day readmissions (2.93% vs. 2.69%) between outpatient versus matched inpatient procedures (all P > 0.05). The only significant finding was a lower rate of blood transfusion in outpatient procedures (0.54%) compared with inpatient procedures (4.02%) (P < 0.001). CONCLUSIONS: The perioperative outcomes assessed here support the conclusion that ORIF for proximal humerus fractures can be performed in the outpatient setting without increased rates of 30-day perioperative complications or readmissions compared with inpatient procedures. However, it is worth noting that the majority of outpatient cases were younger than the average geriatric proximal humerus fracture patient. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Alendronate enhances osseointegration in a murine implant model.

Administration of bisphosphonates following total joint arthroplasty might be beneficial to reduce aseptic loosening. However, their effects on peri-implant bone formation and bone-implant interface strength have not been investigated yet. We used a physiologically loaded mouse implant model to investigate the short-term effects of postoperative systemic alendronate on osseointegration. A titanium implant with a rough surface was inserted in the proximal tibiae of 17-week-old female C57BL/6 mice (n = 44). Postimplantation mice were given alendronate (73 µg/kg/days, n = 22) or vehicle (n = 22) 5 days/week. At 7- and 14-day postimplantation, histology and histomorphometry were conducted. At 28 days, microcomputed tomography and biomechanical testing were performed (n = 10/group). Postoperative alendronate treatment enhanced osseointegration, increasing maximum pullout load by 45% (p < .001) from 19.1 ± 4.5 N in the control mice to 27.6 ± 4.9 N in the treated mice, at day 28 postimplantation. Alendronate treatment increased the bone volume fraction by 139% (p < .001) in the region distal to the implant and 60% (p < .05) in the peri-implant region. At 14-day postimplantation, alendronate treatment decreased the number of osteoclasts per bone perimeter (p < .05) and increased bone volume fraction (p < .01) when compared with the control group. Postimplantation, short-term alendronate treatment enhanced osseointegration as demonstrated by increased bone mass, trabecular bone thickness, and maximum pullout load. Alendronate decreased peri-implant osteoclasts while preserving peri-implant osteoblasts and endothelial cells, in turn, increasing bone volume fraction. This data supports the postoperative clinical use of bisphosphonates, especially in patients with high risks of aseptic loosening.

Trends of Prosthetic Joint Infection Organisms and Recurrence for a Single High-Volume Arthroplasty Surgeon Over 20 Years.

BACKGROUND: Prosthetic joint infection (PJI) is a morbid complication following total joint arthroplasty (TJA). PJI diagnosis and treatment has changed over time, and patient co-management with a high-volume musculoskeletal infectious disease (MSK ID) specialist has been implemented at our institution in the last decade. METHODS: We retrospectively evaluated all consecutive TJA patients treated for PJI between 1995 and 2018 by a single high-volume revision TJA surgeon. Microbial identities, antibiotic resistance, prior PJI, and MSK ID consultation were investigated. RESULTS: In total, 261 PJI patients (median age 66 years, interquartile range 57-75) were treated. One-year and 5-year reinfection rates were 15.8% (95% confidence interval [CI] 11.6-20.7) and 22.1% (95% CI 17.0-27.7), respectively. Microbial identities and antibiotic resistances did not change significantly over time. Despite seeing more prior PJI patients (53.3% vs 37.6%, P = .012), MSK ID-managed patients had similar infection rates as non-MSK ID-managed patients (hazard ratio [HR] 1.02, 95% CI 0.6-1.75, P = .93). Prior PJI was associated with higher reinfection risk (HR 2.39, 95% CI 1.39-4.12, P = .002) overall and in patients without MSK ID consultation, specifically (HR 2.78, 95% CI 1.37-5.65, P = .005). This risk was somewhat lower and did not reach significance in prior PJI patients with MSK ID consultation (HR 1.97, 95% CI 0.87-4.48, P = .106). CONCLUSION: We noted minimal differences in microbial/antibiotic resistances for PJI over 20 years in a single institution, suggesting current standards of PJI treatment remain encouragingly valid in most cases. MSK ID involvement was not associated with lower reinfection risk overall; however, in patients with prior PJI, the risk of reinfection appeared to be somewhat lower with MSK ID involvement. LEVEL OF EVIDENCE: Level IV-Case Series.

Correction to: At the US Epicenter of the COVID-19 Pandemic, an Orthopedic Residency Program Reorganizes.

[This corrects the article DOI: 10.1007/s11420-020-09765-5.].

2020 John Charnley Award: The antimicrobial potential of bacteriophage-derived lysin in a murine debridement, antibiotics, and implant retention model of prosthetic joint infection.

AIMS: Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. METHODS: The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. RESULTS: PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. CONCLUSION: PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3-10.